Safety Study of SGX523, a Small Molecule Met Inhibitor, to Treat Solid Tumors

A Phase I, Multi-Center, Open Label, Dose Escalation, Safety, PK and PkD Study of Orally Administered SGX523, a Small Molecule Anti-Cancer Agent, on a Twice Daily, Uninterrupted Schedule in Patients With Advanced Cancer

SGX523 is a drug which acts by blocking the function of an enzyme called MET. MET activity may be important in growth and survival of some types of cancer. This Phase I trial is studying the safety, side effects, and best dose of SGX523 when given to patients with advanced cancer, and how well it inhibits MET activity in tumors.

Inclusion Criteria:

• Subject has the ability to understand, able, willing to comply with study procedures and follow up visits, and has provided written consent
• Pathologic evidence of solid tumor
• Failed standard therapy and deemed by the Investigator to be suitable for participation into the trial
• Laboratory values (obtained within 10 days prior to enrollment): ANC: >= 1.5 × 109/L; Platelets: >= 100 × 109/L; Hemoglobin: >= 10.0 g/dL (without transfusions); Bilirubin: within normal range; AST, ALT, and alkaline phosphatase: <= 2.5 x ULN without tumor liver involvement; Serum creatinine: within normal limits; Calculated creatinine clearance: >= 60 mL/min/1.73 m2 for patients with creatinine > Institutional Normal Values; PT/PTT/INR: within normal limits..
• Have IHC evidence of phospho-MET expression on tumor material no more than 12 months old. This is a requirement only for entry into the MTD dose expansion phase.
• Have no residual toxic effects of previous therapy, and undergo a washout period of at least 5 half-lives from the time of administration of the previous therapy.

Exclusion Criteria:

• Pregnant, lactating, or may become pregnant
• Cardiac disease requiring medical therapy
• Have had a major surgery within 4 weeks prior to Day 1 of the study
• Have an active, uncontrolled bacterial, viral, or fungal infection that requires ongoing systemic therapy
• Have a known active infection with HIV, hepatitis B or C
• Have psychiatric or seizure disorders that would require therapy or interfere with study participation
• Have other severe concurrent nonmalignant disease that could compromise protocol objectives, including malabsorptive conditions
• Patients receiving prohibited medications as listed in Appendix E, including drugs categorized as strong inhibitors of CYP3A4 and A5 and drugs known to have a high potential risk of liver toxicity
• Have known allergy to SGX523 formulation or its excipients (croscarmellose sodium, lactose monohydrate and magnesium steareate)
• Patients receiving anti-coagulant therapy